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Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational

Anna M Steele1, Kirsty J Wensley, Sian Ellard

  • 1NIHR Exeter Clinical Research Facility, University of Exeter, Exeter, Devon, United Kingdom. anna.steele@pms.ac.uk

Plos One
|June 27, 2013
PubMed

Insights

New age-related HaemoglobinA1c (HbA1c) ranges help identify glucokinase (GCK) mutations, distinguishing them from type 1 and type 2 diabetes. These ranges improve diagnosis for GCK mutation carriers.

Area of Science:

  • Endocrinology
  • Genetics
  • Clinical Diagnostics

Background:

  • HaemoglobinA1c (HbA1c) is a standard for diabetes diagnosis.
  • Fasting plasma glucose (FPG) aids in identifying glucokinase (GCK) mutations causing persistent hyperglycemia.
  • GCK mutations lead to lifelong, persistent fasting hyperglycemia.

Purpose of the Study:

  • Derive age-related HbA1c reference ranges for GCK mutation patients.
  • Assess HbA1c's ability to differentiate GCK mutation carriers from controls and other diabetes types.
  • Determine the proportion of GCK mutation carriers diagnosed with diabetes based on HbA1c and FPG criteria.

Main Methods:

  • Recruited individuals with GCK mutations (n=129), familial controls (n=100), type 1 diabetes (T1D, n=278), and type 2 diabetes (T2D, n=319), all aged ≥18 years.
  • Utilized Receiver Operating Characteristic (ROC) analysis to evaluate HbA1c and FPG discrimination effectiveness.
  • Established age-specific HbA1c reference ranges for GCK mutation subjects.

Main Results:

  • Age-related HbA1c ranges for GCK mutations: 38-56 mmol/mol (≤40 years) and 41-60 mmol/mol (>40 years).
  • All GCK mutation patients (100%) exceeded the lower limit of their age-appropriate HbA1c range, while 69% of controls fell below.
  • HbA1c effectively discriminated GCK mutations from T1D/T2D, with 97% accuracy using upper limits; HbA1c (≥48 mmol/mol) diagnosed more GCK cases than FPG (≥7 mmol/l).

Conclusions:

  • Current HbA1c criteria may overdiagnose diabetes in GCK mutation patients.
  • Derived age-related HbA1c ranges aid in distinguishing GCK mutation-related hyperglycemia.
  • These ranges facilitate the identification of GCK mutation carriers for genetic testing.
Abstract

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